ICP47 is an immediate early gene product of herpes simplex virus (HSV) which has been shown to be responsible for rendering HSV-infected human fibroblasts resistant to lysis by cytotoxic T lymphocytes (CTL). The mechanism underlying its action has been shown to be secondary to it binding to the cellular TAP proteins which are involved in class I restricted antigen processing. By inhibiting transport of peptides to the endoplasmic reticulum (E-R) by TAP, ICP47 prevents presentation of peptide-class I MHC complexes on the cell surface and hence renders the cell resistant to CTL lysis. The biological relevance of this mechanism in vivo is not known though it may contribute to immune escape and establishment of latency in HSV-infected humans. HSV is being evaluated in animal studies in rhesus macaques for its suitability as a vector for SIV vaccines. Our aim was to analyze the role of ICP47 on antigen presentation in rhesus macaques, as theoretically its effect could render a HSV-based vaccine ineffectual by masking it from CTL recognition. Because ICP47 does not block TAP function in mice, in vivo analysis of the effect of ICP47 cannot be carried out in murine models. The effect of ICP47 on CTL recognition in rhesus macaques was assessed in vitro in CMV-specific and SIV-specific CTL assays. Target cells were infected with recombinant adenovirus or vaccinia - ICP47 vectors for 24 hours prior to infection with specific antigen. The effect of double infection with ICP47 on specific lysis was assessed in standard 51 chromium release assays. In multiple experiments, ICP47 reduced CTL lysis by about 50% in CMV-infected rhesus fibroblasts but did not completely abolish CTL recognition. Surface expression of class I MHC on rhesus fibroblasts was reduced ten-fold by ICP47 as assessed by flow cytometric analysis. In peptide transport inhibition assays, ICP47 inhibited peptide transport in rhesus fibroblasts but this inhibition appeared less efficient than in human fibroblasts. These results suggest that the effect of the herpesvirus protein ICP47 on induction of class I-restricted CTL responses in vivo